New Technique Allows Scientists to Monitor Cell Communication

December 10, 2009 - Researchers have discovered a technique that allows scientists to monitor communication between cells for the first time and could revolutionize the way laboratory medical experiments are conducted. The method is likely to make laboratory studies of cancers and other human diseases, and assessment of new drugs to target them, more accurate.

The technique was developed by Dr. Tony Pawson, Senior Investigator at the Samuel Lunenfeld Research Institute of Mount Sinai Hospital in Toronto, along with Dr. Rune Linding at The Institute of Cancer Research (ICR) in the United Kingdom. The research is published in the latest edition of the journal Science.

The study’s authors say that understanding how cells talk to each other is crucial, as many cancers and other diseases are caused by a breakdown in such communications systems. The researchers have developed a way to more accurately replicate and monitor what’s happening in the body. Before, scientists could only hear a monologue from one cell to another, but with this new technique, for the first time it is possible to assess the outcome of a conversation between cells.

Until now, scientists have generally studied cell communication by taking a single population of cells, adding a molecule to stimulate the cells, and measuring the response. But this technique does not take into account that tissues in the body require reciprocal signals between different types of cells, like a conversation between people.

“This technique, which lets us consider two cell populations at once, is a major step towards more accurate laboratory research,” explains Dr. Pawson. “We will adopt this approach to study how distinct cell populations talk to one another in diseases like cancer; the next stage is to find a way to take even more cell types and molecules into account. We can’t mimic what goes on in the body yet, but we are getting closer.”

The new method involves growing cells in media containing labelled amino acids (the fundamental building blocks of proteins) that are incorporated into the cells’ proteins. Two cell types, grown with different labels, are then combined for a short time to allow them to talk to each other, and then the cells are broken open so the proteins produced can be examined. A technique called mass spectrometry is then used to measure the level of each label, showing from which cell type the proteins originated.

The team then looked for genes that were involved in the conversation from a functional point of view. They tested about 10 per cent of all human genes by blocking them within the cells one by one, using small interfering RNA molecules, and measured whether the cells behaved differently. Information about the proteins and genes was used to make a computer model of the signalling networks involved – effectively highlighting the important points in the conversation.

The research team first used this technique to study a key receptor protein, known as EphB2, which acts like an antenna to position cells precisely within the body, and is important for maintaining boundaries between tissues. Cells with EphB2 communicate with a distinct set of cells making another protein, termed ephrin-B1, and the researchers have used their technique to identify bidirectional signals between these two cell populations. Cancer cells need to cross tissue boundaries to spread throughout the body, so defects in this system can promote metastasis.

“Many types of cancers – including colorectal cancer, lung, prostate and breast cancer and glioma - have an abnormality in the Eph communications system, and it may also play a role in other diseases. However, until now it has not been possible to study this network during cell-to-cell contact, the most crucial time,” says Dr. Claus Jørgensen, co-author and post doctoral fellow at The Samuel Lunenfeld Research Institute of Mount Sinai Hospital.
The study was funded in part by Genome Canada through the Ontario Genomics Institute.

“This research heralds the next level in understanding proteomic systems and their role in modulating the interactions between different populations of cells,” commented Dr. Christian Burks, President and CEO of Ontario Genomics Institute (OGI). “By combining lineage-specific labeling with mass spectrometric identification and quantification, their international team has created an approach that could be used to monitor more complex effects of potential new therapies, which in some cases would represent a more useful readout on their potential for tackling metastatic cancers in the context of drug discovery.”

In 2008, Dr. Pawson was honoured with the Kyoto Prize, an international award that honours whose who have contributed significantly to the scientific, cultural and spiritual betterment of humankind. In 2006, Dr. Pawson was inducted into the Canadian Medical Hall of Fame, the same year that he was named to the Order of the Companions of Honour by her Majesty Queen Elizabeth II, one of only nine Canadians to have received such an honour. For more information, please see http://pawsonlab.mshri.on.ca/

Note to editors:
• The cells studied expressed either the EphB2 receptor or the corresponding ephrinB1 ligand.

About the Samuel Lunenfeld Research Institute of Mount Sinai Hospital

The Samuel Lunenfeld Research Institute of Mount Sinai Hospital, a University of Toronto affiliated research centre established in 1985, is one of the world's premier centres in biomedical research. Thirty-four principal investigators lead research in diabetes, cancer biology, epidemiology, stem cell research, women's and infants' health, neurobiology and systems biology. For more information on the Samuel Lunenfeld Research Institute, please visit www.lunenfeld.ca.

About the Institute of Cancer Research (ICR)

The ICR is Europe’s leading cancer research centre.

The ICR has been ranked the UK’s top academic research centre, based on the results of the Higher Education Funding Council’s Research

ssessment Exercise.

The ICR works closely with partner The Royal Marsden NHS Foundation Trust to ensure patients immediately benefit from new research. Together the two organisations form the largest comprehensive cancer centre in Europe.

The ICR has charitable status and relies on voluntary income, spending 95 pence in every pound of total income directly on research.

As a college of the University of London, the ICR also provides postgraduate higher education of international distinction.

Over its 100-year history, the ICR’s achievements include identifying the potential link between smoking and lung cancer which was subsequently confirmed, discovering that DNA damage is the basic cause of cancer and isolating more cancer-related genes than any other organisation in the world.